What is the molecular pathology of low-risk prostate cancer?

Objectives: Low-risk prostate cancer is defined as a clinical T1c or T2a tumor with a Gleason score of ≥6 and PSA <10 ng/ml. This is a pretreatment diagnosis and the patient can turn out to have either significant or insignificant disease. With methods currently available in practice it may not be possible to differentiate between these groups. Numerous molecular pathological changes have been described in prostate carcinoma. This review was to evaluate which of these changes may be useful to distinguish the group of patients likely to have significant carcinoma within the low risk category. Materials and methods: The literature on molecular pathology of prostate cancer was reviewed using MEDLINE and reference lists of relevant publications focusing on early and late molecular events and available molecular biomarkers in prostate cancer. Results: There are a variety of molecular markers with the potential to be clinically utilized for assessment of low risk prostate cancer. One of the most promising is TMPRSS2: ETS fusion, which is a homogeneous event occurring early in prostate carcinogenesis. Other promising markers include p27, EZH2 and c-MYC. Conclusions: FISH analysis or RT-PCR based assays to detect TMPRSS2: ETS fusion and immunohistochemical assessment of p27, EZH2 and c-MYC may become useful ancillary tests in patients with low risk prostate cancer. Some serum biomarkers have promise for future use. Large prospective studies followed by clinical trials are necessary before these molecular markers could be integrated into clinical practice.